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Pilot Study of a Next-Generation Sequencing-Based Targeted Anticancer Therapy in Refractory Solid Tumors at a Korean Institution

Authors
 Hyung Soon Park  ;  Sun Min Lim  ;  Sora Kim  ;  Sangwoo Kim  ;  Hye Ryun Kim  ;  KyuBum Kwack  ;  Min Goo Lee  ;  Joo-Hang Kim  ;  Yong Wha Moon 
Citation
 PLoS One, Vol.11(4) : e0154133, 2016 
Journal Title
 PLoS One 
Issue Date
2016
MeSH
Adult ; Aged ; Antineoplastic Agents/therapeutic use* ; Asian Continental Ancestry Group/genetics ; Class I Phosphatidylinositol 3-Kinases ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Everolimus/therapeutic use ; Feasibility Studies ; Female ; Genetic Predisposition to Disease/genetics ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/methods* ; Mutation ; Neoplasms/drug therapy* ; Neoplasms/ethnology ; Neoplasms/genetics ; Niacinamide/analogs & derivatives ; Niacinamide/therapeutic use ; Phenylurea Compounds/therapeutic use ; Phosphatidylinositol 3-Kinases/genetics ; Pilot Projects ; Precision Medicine/methods ; Proto-Oncogene Proteins B-raf/genetics ; Quinazolines/therapeutic use ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Republic of Korea ; Young Adult
Abstract
We evaluated the preliminary efficacy and feasibility of a next-generation sequencing (NGS)-based targeted anticancer therapy in refractory solid tumors at a Korean institution. Thirty-six patients with advanced cancer underwent molecular profiling with NGS with the intent of clinical application of available matched targeted agents. Formalin-fixed paraffin-embedded (FFPE) tumors were sequenced using the Comprehensive Cancer Panel (CCP) or FoundationOne in the Clinical Laboratory Improvement Amendments-certified laboratory in the USA. Response evaluations were performed according to RECIST v1.1. Four specimens did not pass the DNA quality test and 32 specimens were successfully sequenced with CCP (n = 31) and FoundationOne (n = 1). Of the 32 sequenced patients, 10 (31.3%) were ≤40 years. Twelve patients (37.5%) had received ≥3 types of prior systemic therapies. Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease). Nineteen of 24 patients with actionable mutations could not undergo targeted therapy based on genomic testing because of declining performance status (10/24, 41.7%), stable disease with previous treatment (5/24, 20.8%), and lack of access to targeted medication (4/24, 16.7%). NGS-based targeted therapy may be a good option in selected patients with refractory solid tumors. To pursue this strategy in Korea, lack of access to clinical-grade NGS assays and a limited number of genotype-matched targeted medications needs to be addressed and resolved.
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DOI
10.1371/journal.pone.0154133
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
Yonsei Authors
김상우(Kim, Sangwoo)
김혜련(Kim, Hye Ryun) ORCID logo https://orcid.org/0000-0002-1842-9070
박형순(Park, Hyung Soon)
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152480
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